Kinins are potent vasodilators which may regulate blood pressure either by their direct vasodilator effect, or indirectly by regulating renal function. Circulating kinins (blood kinins) are released from plasma kininogen by either plasma or glandular kallikrein, or both. These two enzymes are immunochemically and functionally unrelated. We plan to determine whether plasma or glandular kallikrein, or both, are responsible for the formation of blood kinins. Inhibition of kininase II (angiotensin converting enzyme) results in a decrease of blood pressure in some clinical and experimental situations. This vasodepressor effect has been attributed to inhibition of the conversion of angiotensin I to angiotensin II and to inhibition of kinins destruction. However, the evidence relating kinins to the decrease of blood pressure produced by converting enzyme inhibitor (CE inh) is only indirect. We will investigate the role of kinins in the hypotensive effect of CE inh. Previous studies have shown a poor correlation between urinary kallikrein and intrarenal formation of kinins; we will investigate factors that control the intrarenal formation of kinins. Kinins released by renal kallikrein may be important in regulating renal function. The effects of kinin inhibition in the excretion of water and electrolytes will be examined. We also intend to determine whether the conspicuously low kallikrein excretion observed in Dahl S rats (rats bred for their susceptibility to the hypertensive effect of salt) is partially due to the excretion of either kallikrein bound to inhibitors or to inactive prekallikrein. Finally, we will study the role of the sympathetic nervous system in the regulation of kallikrein excretion. These studies will help to elucidate the role of the kallikrein-kinin system in the regulation of renal function and blood pressure.